Contemporary aspects of the biology and therapeutic regulation of the microsomal triglyceride transfer protein.
نویسندگان
چکیده
The microsomal triglyceride transfer protein (MTP), the product of the MTTP gene, is essential for the assembly and secretion of apolipoprotein B-containing lipoproteins, but when defective causes abetalipoproteinemia. Abetalipoproteinemia is a rare autosomal recessive disorder characterized by the inability to produce chylomicrons or very low-density lipoproteins, with the absence of apolipoprotein B-containing lipoproteins in the circulation. Knowledge of the molecular basis for abetalipoproteinemia has led to the development of therapies for dyslipidemia that inhibit MTP. Partial MTP inhibition using small molecule inhibitors, such as lomitapide, can effectively lower plasma low-density lipoprotein-cholesterol and apolipoprotein B levels, but is associated with gastrointestinal side effects and hepatic steatosis, whose long-term sequelae remain unclear; lomitapide has accordingly only been approved as a treatment for homozygous familial hypercholesterolemia. Intestine-specific inhibitors of MTP decrease chylomicron biogenesis and improve insulin sensitivity in experimental animals and, while overcoming hepatic steatosis, may have significant gastrointestinal side effects that could limit their use in humans. We review contemporary aspects of the biology and therapeutic regulation of MTP and their significance for lipid metabolism and cardiovascular disease.
منابع مشابه
Anti-hypercholesterolemic Effect of Berbamine Isolated from Rhizoma Coptidis in Hypercholesterolemic Zebrafish Induced by High-Cholesterol Diet
The anti-hypercholesterolemic effect of berbamine (BBM) isolated from Rhizoma Coptidis (RC) was investigated in hypercholesterolemic zebrafish model induced by high-cholesterol (HC) diet. Zebrafish embryo assay revealed no significant difference in morphology and cell death with the treatment of BBM less than 20 μg/mL. In zebrafish larvae, the fluorescently labeled cholesterol in caudal artery ...
متن کاملAnti-hypercholesterolemic Effect of Berbamine Isolated from Rhizoma Coptidis in Hypercholesterolemic Zebrafish Induced by High-Cholesterol Diet
The anti-hypercholesterolemic effect of berbamine (BBM) isolated from Rhizoma Coptidis (RC) was investigated in hypercholesterolemic zebrafish model induced by high-cholesterol (HC) diet. Zebrafish embryo assay revealed no significant difference in morphology and cell death with the treatment of BBM less than 20 μg/mL. In zebrafish larvae, the fluorescently labeled cholesterol in caudal artery ...
متن کاملApelin: A promising therapeutic target? (Part 1)
Apelin is a recently discovered bioactive peptide, known to be an endogenous high-affinity ligandfor the previously orphan G protein-coupled receptor APJ. Apelin/APJ as a novel signaling pathwayhas been shown to play many crucial roles in cardiovascular function, blood pressure regulation, fluidhomeostasis, feeding behavior, obesity, type 2 diabetes mellitus, adipoinsular axis regulation, cellp...
متن کاملHepatic expression of microsomal triglyceride transfer protein and in vivo secretion of triglyceride-rich lipoproteins are increased in obese diabetic mice.
Secondary hyperlipidemia is a major cardiovascular risk factor in individuals with type 2 diabetes. Increased hepatic production of apolipoprotein B (apoB)-containing lipoproteins contributes to the elevated plasma levels, but the mechanism is poorly understood. Recent results have established that microsomal triglyceride transfer protein (MTP) is rate limiting for the assembly and secretion of...
متن کاملEffects of T208E activating mutation on MARK2 protein structure and dynamics: Modeling and simulation
Microtubule Affinity-Regulating Kinase 2 (MARK2) protein has a substantial role in regulation of vital cellular processes like induction of polarity, regulation of cell junctions, cytoskeleton structure and cell differentiation. The abnormal function of this protein has been associated with a number of pathological conditions like Alzheimer disease, autism, several carcinomas and development of...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation research
دوره 116 1 شماره
صفحات -
تاریخ انتشار 2015